Testosterone replacement therapy (TRT) has come a long way from the days when men had only a few options—often painful injections or messy gels—to treat low testosterone. Low‑T, or hypogonadism, can sap energy, reduce muscle mass, dull the mind and diminish sexual desire. Conventional therapies bring relief but have important limitations: injections produce hormone spikes and crashes, gels can transfer to family members, patches irritate the skin and all exogenous testosterone suppresses natural production. These drawbacks, along with increasing awareness of low testosterone and an expanding telemedicine market, have spurred a wave of innovation. Today researchers and clinicians are reimagining how testosterone can be delivered, monitored and regulated, ushering in a new era of therapies that promise greater convenience, personalization and safety. This article demystifies those emerging therapies and explains what men in the United States need to know.

Understanding Modern TRT: The Starting Point

Before exploring cutting‑edge treatments, it’s important to grasp the baseline. The Cleveland Clinic identifies six main delivery systems for testosterone: intramuscular injections, subcutaneous injections, topical gels, patches, implanted pellets and buccal or nasal formulations. Each method has benefits and drawbacks:

• Injections (typically testosterone cypionate or enanthate) deliver high doses every one to two weeks. While effective, they cause sharp peaks and troughs in blood levels, leading to mood swings and polycythemia (thickened blood). Large injections must be administered in clinics or require self‑injection training.
  
• Topical gels and patches offer steadier daily dosing but risk transferring hormone to partners and often irritate skin. Men must avoid contact with women or children until the product dries.
  
• Pellet implants involve inserting small cylinders under the skin that release hormone for months. They avoid daily maintenance but require minor surgery and carry risk of infection or extrusion.
  
• Buccal tablets and nasal gels provide alternatives for men who dislike injections or skin applications, though dosing frequency can be high.
  

Regardless of delivery method, TRT is not for everyone. The U.S. Food and Drug Administration (FDA) approves testosterone therapy only for men with clinically low levels due to underlying medical conditions—not for age‑related decline. Candidates undergo morning testosterone testing and evaluation of hemoglobin, hematocrit, liver enzymes and prostate‑specific antigen (PSA) before starting therapy. Men with prostate cancer, breast cancer, severe heart failure or untreated sleep apnea should avoid TRT because it may exacerbate these conditions. Even approved patients must watch for side effects such as acne, fluid retention, gynecomastia, prostate enlargement, worsening sleep apnea, testicular shrinkage, skin irritation (for topical therapies) and decreased sperm production.

Recent regulatory updates illustrate the evolving safety landscape. Results from the TRAVERSE trial showed that TRT did not increase major adverse cardiovascular events compared with placebo; accordingly, in February 2025 the FDA removed the boxed warning about heart attacks and strokes from testosterone labels. However, new warnings emphasize that testosterone can raise blood pressure and maintain strict limitations against prescribing it for age‑related low testosterone. Understanding this context helps explain why next‑generation therapies focus not only on convenience but also on improving safety and personalization.

Why Do We Need New Therapies?

Conventional TRT works for many men, but it has clear shortcomings that drive innovation:

1. Hormone fluctuations – Large injections cause spikes and troughs. Gels provide steadier levels but still fluctuate with daily application.
   
2. Administration burden – Frequent clinic visits for injections or daily dosing can be inconvenient; pellets require minor surgery.
   
3. Side effects and transfer risk – High hormone peaks increase the risk of polycythemia and mood swings, while gels may transfer to partners and irritate skin.
   
4. Suppression of natural production – All exogenous testosterone suppresses the hypothalamic–pituitary–gonadal axis, lowering LH and FSH and reducing sperm production.
   
5. Limited personalization – Conventional dosing protocols often ignore individual variations in metabolism, genetics and lifestyle.
   

Emerging therapies aim to mitigate these issues by delivering hormones more consistently, supporting endogenous production or harnessing digital tools to tailor dosing. Below we examine the most promising innovations and what they mean for patients.

Microdosing and Extended‑Release Injections

One of the simplest yet most impactful innovations is the shift to microdosing protocols. Instead of injecting 100–200 mg of testosterone every two weeks, microdosing administers smaller doses (10–40 mg) multiple times per week subcutaneously. MenMD, a men’s health clinic, notes that this approach smooths out hormonal peaks and troughs and reduces side effects like mood swings and thickened blood. Microdosing kits often include user‑friendly syringes and AI‑enabled smartphone apps that send dosing reminders and record administrations. Some clinics offer programmable pens that adjust injection depth and link with digital diaries, further simplifying self‑administration.

For men who prefer fewer injections, extended‑release formulations deliver testosterone slowly over several weeks. MenMD explains that new subcutaneous formulations use carriers that allow injections every 10–14 days with more stable serum levels compared with old intramuscular shots. These products reduce clinic visits and may appeal to men who travel frequently.

What Patients Should Ask

When considering microdosing or extended‑release injections, ask your provider:

• How often will I need to inject? Microdosing may require 2–3 shots per week; extended‑release might be every 1–2 weeks.
  
• What training is provided? Proper technique ensures consistent absorption and minimizes injection site irritation.
  
• How will my dosing be adjusted? Providers should track blood levels and symptoms to fine‑tune dosing.
  

Advancements in Transdermal Therapies

Topical therapies remain popular because they avoid needles. Innovators are improving both the drugs and the delivery vehicles:

Enhanced Gels and Patches

New gel formulations employ microemulsion technology to enhance absorption and reduce transfer risk. MenMD notes that these gels use stabilizers and lipophilic carriers that increase penetration while drying faster, so they are less likely to rub off on partners. Meanwhile, modern patches use adhesive materials that cause less irritation and deliver hormone more consistently. Some patches incorporate microneedles that create tiny channels, increasing absorption without causing pain.

Nasal Gels and Buccal Systems

Emerging delivery routes include nasal gels, which deliver testosterone through the nasal mucosa, achieving rapid absorption and avoiding first‑pass liver metabolism. These are ideal for men who want quick, needle‑free dosing but are comfortable with multiple applications per day. Another option is the buccal tablet—a small adhesive applied to the gum that releases testosterone slowly across the oral mucosa; it must be replaced twice daily. Future products may include thin buccal films that provide 24‑hour release.

Patient Considerations

Men evaluating transdermal therapies should weigh:

• Skin sensitivity – If you have eczema or allergies, ask about hypoallergenic formulas.
  
• Transfer risk – Follow application instructions carefully to avoid exposing partners.
  
• Dosing frequency – Topical therapies require discipline; missing doses can lead to symptoms returning.
  

Next‑Generation Oral Testosterone

Historically, oral testosterone failed because the liver degraded most of the hormone, reducing efficacy and risking liver damage. Innovations have revived oral therapies:

Lymphatic Absorption: Kyzatrex

The approval of testosterone undecanoate soft gel capsules (Kyzatrex) represents a major shift. These capsules use a lipid‑based formulation that promotes absorption through the lymphatic system rather than the liver, achieving about 90 % bioavailability compared with 3–5 % in earlier oral preparations. Clinical studies show that Kyzatrex maintains serum testosterone within the normal range for more than 87 % of patients and causes minimal liver enzyme elevations. For men who dislike injections or daily gels, an oral capsule taken 2–3 times per day may offer a convenient alternative.

Soft Gel Capsules and Nasal Spray TU

A 2023 systematic review highlighted additional innovations: a new oral soft gel formulation of testosterone undecanoate (TU) that produces steady levels and nasal testosterone gel that provides consistent dosing when administered multiple times per day. These products aim to combine convenience with stable pharmacokinetics; however, patients must adhere to daily dosing schedules. Importantly, long‑acting TU injections also produce steady state levels and are being explored to reduce dosing frequency.

Questions for Patients

• How many pills or sprays will I need daily? Some oral capsules require 2–3 doses per day; nasal gels may need thrice‑daily application.
  
• Will my insurance cover it? Oral therapies can be more expensive than injections or gels and may not be covered.
  
• What are the side effects? Some users report gastrointestinal upset or headaches; discuss these with your doctor.
  

Implant and Microbead Technologies

Improved Pellets

Traditional pellet implants release testosterone over 3–6 months. Recent improvements include smaller pellet sizes and modified release kinetics that provide steadier hormone levels and fewer insertion complications. Some companies are researching bioabsorbable pellets that dissolve over time, eliminating the need for removal.

Hydrogel Microbeads: A Breakthrough

One of the most exciting developments is injectable hydrogel microspheres, often called microbeads. The biotech company Likarda developed a core‑shell spherification (CSS) process that forms microspheres completely in water, avoiding oil emulsions that previously contaminated pellets. These microbeads encapsulate testosterone in a hydrophilic polymer such as hyaluronic acid or alginate. Because the hormone is embedded in a slowly degrading hydrogel, it is not exposed immediately to tissue, reducing local irritation; as the hydrogel breaks down, testosterone diffuses gradually into the bloodstream. Early data suggest that depending on the hydrogel design, the half‑life of a hormone can be extended from 12 hours to 10 days or longer. Microbeads act like “micropellets” that deliver extended release without surgery.

Researchers are exploring 3D printing methods to produce these microbeads at scale. One technique uses an electromagnetic droplet printer to deposit tiny alginate droplets containing liposomal drug suspensions into a calcium bath, where they cross‑link to form uniform spheres. Controlling the viscosity of the printing ink (100–250 mPa·s) ensures reproducible droplet formation, while adjusting nozzle frequency and amplitude determines bead size. These manufacturing advances could make injectable microbeads a mainstream therapy in the next decade.

Patient Considerations

• Availability – Microbead therapies are still experimental and not yet widely available. Ask your provider if clinical trials exist.
  
• Injection frequency – Early prototypes suggest monthly or even quarterly injections. This convenience is a key advantage over weekly shots or daily gels.
  
• Safety and long‑term data – Because microbeads are new, long‑term safety data are limited. Discuss risks versus benefits and ensure any use is within a regulated clinical trial.
  

SERMs: Boosting Your Own Testosterone

Exogenous testosterone suppresses natural production by inhibiting LH and FSH. Selective estrogen receptor modulators (SERMs) represent an alternative. Drugs like clomiphene citrate and enclomiphene block estrogen receptors, stimulating the hypothalamus and pituitary to increase LH/FSH secretion and thereby boosting endogenous testosterone. MenMD highlights that SERMs are attractive for younger men or those wanting to preserve fertility because they maintain sperm production.

In a 2024 retrospective study, men who switched from clomiphene to its isomer enclomiphene achieved a median testosterone increase of 166 ng/dL compared with 98 ng/dL on clomiphene and experienced fewer estrogen‑related side effects. While not FDA‑approved for hypogonadism, enclomiphene is prescribed off‑label and may become more common as research mounts. Patients considering SERMs should consult fertility specialists and undergo regular hormone monitoring.

AI‑Driven Personalization and Remote Monitoring

Personalized Dosing Algorithms

Personalization is a defining theme of next‑generation TRT. The Regenerative Medical Therapy clinic describes using artificial intelligence (AI) to analyze hormone levels, genetic profiles, body composition, sleep patterns, diet and stress to craft individualized dosing plans. Machine‑learning models learn how an individual metabolizes testosterone and adjust doses in real time. Some clinics integrate wearable devices and smartphone apps that track heart rate, sleep, activity and stress, feeding data into AI systems for dynamic dose adjustments.

Telehealth Platforms and At‑Home Testing

Telehealth has exploded in popularity, and TRT is no exception. Services like TRTNYC allow men to complete an initial consultation online, order at‑home blood or saliva tests, and receive prescriptions digitally. The process typically involves filling out a health questionnaire, scheduling a video appointment with a physician, collecting samples with a mail‑in kit and then discussing results and treatment options via video. Medications are shipped to the patient’s door, and follow‑up visits occur virtually.

Remote monitoring extends beyond consultations. Men can send blood pressure readings, hematocrit levels and symptom logs via secure apps. Providers can adjust dosing or order additional labs from afar. Telehealth offers convenience, privacy and access to specialists, though not all treatments are available in every state due to licensing restrictions.

Advantages and Caveats

Advantages:

• Convenience: No need for regular office visits. At‑home kits simplify lab testing.
  
• Privacy: Men can address sensitive hormonal issues discreetly.
  
• Access: Telehealth connects patients with specialists outside their immediate geographic area.
  

Caveats:

• Insurance: Some telehealth clinics operate on subscription models; ensure you understand costs.
  
• Regulatory differences: Telemedicine laws vary by state; certain treatments (e.g., controlled substances) may be restricted.
  
• Quality of care: Choose reputable providers with board‑certified physicians and evidence‑based protocols.
  

Gene Therapy and Beyond

While most new therapies modify how testosterone is delivered, some aim to cure hypogonadism by restoring endogenous production. Researchers from Tulane University and the Mayo Clinic developed an AAVDJ‑Lhcgr gene therapy that delivers the luteinizing hormone/choriogonadotropin receptor (Lhcgr) gene to Leydig cell progenitors in mice. The AAVDJ vector penetrated these progenitors more efficiently than previous vectors and restored natural testosterone production and fertility, along with improved muscle, bone and adipose tissue function. Though human trials are years away, this research points to the possibility of a one‑time treatment that could permanently correct certain forms of primary hypogonadism.

Developing gene therapies requires advanced manufacturing techniques. A review on adeno‑associated virus (AAV) production describes multiple platforms: viral infection‑based mammalian systems, stable producer cell lines, transient transfection of HEK293 cells with three plasmids (one carrying the gene of interest, another carrying replication and capsid genes and a third providing helper functions), and the baculovirus expression vector system (BEVS) using insect cells. Each method has trade‑offs in yield, scalability, cost and regulatory complexity. As gene therapy moves toward clinical application, manufacturing improvements will be critical.

Microbiome and Stem‑Cell Approaches

Beyond gene therapy, scientists are exploring microbiome modulation and stem‑cell–derived Leydig cells to stimulate endogenous testosterone. Regenerative Medical Therapy notes that these approaches are in very early stages but could one day allow clinicians to manipulate gut bacteria or transplant lab‑grown Leydig cells to increase natural testosterone production. While exciting, these concepts remain experimental and will require years of research before reaching clinical practice.

Regulatory and Safety Considerations

Emerging therapies must navigate a complex regulatory landscape. Patients should be aware that:

1. FDA approval – Most new delivery systems (e.g., microbeads, gene therapy) are not yet FDA‑approved. Use caution with treatments offered outside clinical trials.
   
2. Labeling changes – The FDA’s 2025 update removed the boxed cardiovascular warning but added blood pressure warnings. Providers should monitor blood pressure and hematocrit regularly.
   
3. Long‑term safety – New formulations (e.g., oral soft gels, microbeads) must demonstrate long‑term safety through rigorous trials. Patients should ask about the evidence supporting any proposed treatment.
   
4. Insurance coverage – Some innovations may be expensive and not covered by insurance. Telehealth services often operate via subscriptions.
   
5. Ethical use of AI – AI‑driven dosing and monitoring raise concerns about data privacy, algorithmic bias and accountability. Select providers that employ robust data security and human oversight.
   

Conclusion

Testosterone therapy is evolving rapidly. Innovations such as microdosing injections, improved gels and patches, novel oral capsules like Kyzatrex, implantable microbeads, SERMs and AI‑driven personalization promise to make TRT more effective, convenient and patient‑centered. Telehealth platforms expand access, while cutting‑edge research into gene therapy and microbiome modulation hints at future cures rather than lifelong management. However, these advancements also bring uncertainties. Not all new therapies are FDA‑approved, and long‑term safety data are limited. Men considering TRT should consult qualified healthcare providers, undergo appropriate testing and choose treatments with proven efficacy and safety. By understanding the science behind emerging therapies, patients can make informed decisions and unlock the full potential of next‑generation testosterone care.

Frequently Asked Questions (FAQs)

What makes microdosing different from traditional injections?

Microdosing delivers smaller amounts of testosterone more frequently, providing smoother hormone levels and reducing side effects like mood swings and polycythemia.

Are oral testosterone capsules safe?

New formulations like Kyzatrex use lymphatic absorption to achieve high bioavailability and have shown minimal liver toxicity. However, patients should take them multiple times per day and monitor for side effects.

What are hydrogel microbeads, and are they available?

Hydrogel microbeads are injectable microspheres that release testosterone slowly as the hydrogel degrades. They are currently experimental and may become available through clinical trials; ask your provider about eligibility.

Do SERMs like enclomiphene replace TRT?

SERMs stimulate your body to produce its own testosterone and preserve fertility. In a retrospective study, enclomiphene raised testosterone more and caused fewer side effects than clomiphene. While not FDA-approved for hypogonadism, they may be used off-label under medical supervision.

How does AI personalize testosterone therapy?

AI systems analyze hormone levels, genetics, lifestyle factors, and wearable data to tailor dosing and monitor progress. These tools help physicians adjust treatment dynamically but rely on robust data security.

Is gene therapy for low testosterone available now?

Not yet. Preclinical studies using an AAVDJ-Lhcgr vector restored testosterone production and fertility in mice. Human trials are years away, but this research highlights future possibilities.

Can I get TRT through telehealth?

Yes. Services like TRTNYC offer online consultations, at-home lab kits, digital prescriptions, and remote monitoring. Ensure the provider is licensed in your state and follow up regularly.

What are the risks of emerging TRT therapies?

New therapies may have unknown long-term effects. Microbeads, novel oral preparations, and AI protocols must be studied further. Always discuss benefits and risks with your physician and seek treatments backed by clinical evidence.